Sonodynamic CoMg-Quercetin Nanozyme for Antibacterial Therapy and Multifunctional Bone Regeneration in Infectious Bone Defects.

Abstract

Infectious bone defects remain a serious clinical challenge because infection-associated inflammation markedly hinders bone regeneration. To address this complicated pathological condition, a porphyrin-doped cobalt-magnesium bimetallic quercetin-based sonosensitive nanozyme (CoMg-Que) was engineered to integrate antibacterial therapy, redox modulation, and tissue regenerative functions within a single platform. Upon ultrasound (US) irradiation, CoMg-Que was activated and efficiently generated reactive oxygen species (ROS) for sonodynamic antibacterial treatment. Following termination of US stimulation, its inherent superoxide dismutase- and catalase-like activities further removed excessive ROS, thereby relieving inflammatory responses and re-establishing redox homeostasis. In vitro experiments demonstrated that CoMg-Que effectively eliminated methicillin-resistant Staphylococcus aureus (MRSA) and exhibited favorable immunomodulatory, pro-angiogenic, and osteogenic properties. In an MRSA-infected rat calvarial defect model, CoMg-Que achieved an antibacterial efficiency of 95.24% and markedly enhanced bone regeneration, with the bone volume fraction reaching 26.76%. These findings indicate that CoMg-Que may serve as a promising multifunctional platform for infectious bone defect treatment through coordinated antibacterial, immunoregulatory, and regenerative activities.